Natural Products as Starting Materials for Development of Second Generation Serca Inhibitors Targeted Towards Prostate Cancer Cells

An analysis of the binding of the 8 O N tert butoxycarbonyl 12 aminododecanoyl derivative of 8 O debutanoylthapsigargin to the target molecule, the SERCA pump, has revealed the importance of the length and flexibility of the side chain attached to O 8. Based on the analysis a series of analogues to the 2 unsubstituted analogue trilobolide has been constructed and shown to be equipotent with thapsigargin as SERCA inhibitors. Only the 12 Boc aminododecaonoyl derivative, however, was found to be apoptoti